Histone modifications are implicated in influencing gene expression. To map the human epigenomes at high resolution, we have developed a technique termed ChIP-Seq by combining the chromatin immunoprecipitation assays (ChIP) with the Solexa 1G high throughput sequencing technology. We have generated high-resolution maps for the genome-wide distribution of 20 histone lysine and arginine methylations as well as histone variant H2A.Z, RNA polymerase II and the insulator binding protein CTCF across the human genome using ChIP-Seq. Typical patterns of histone methylations exhibited at promoters, insulators, enhancers and transcribed regions are identified. The monomethylation of H3K27, H3K9, H4K20, H3K79 and H2BK5 are all linked to gene activation, whereas trimethylation of H3K27, H3K9 and H3K79 are linked to repression. H2A.Z associates with functional regulatory elements and CTCF marks boundaries of histone methylation domains. Chromosome banding patterns are correlated with unique patterns of histone modifications. Chromosome breakpoints detected in T cell cancers frequently reside in chromatin regions associated with H3K4 methylations. Our data provide new insights into the function of histone methylation and chromatin organization in genome function.